Handling method of body fluid sample and analysis apparatus using the same

ABSTRACT

Sample sampling to an analysis apparatus  200  or  820  for analyzing a biochemical analysis item is performed by a pipetting device  202  or  840  which uses a repetitively used pipette nozzle, and sample sampling to an analysis apparatus  100  or  810  for analyzing an immune analysis item is performed by a pipetting device  102  or  830  which uses a disposable nozzle tip. A sample bottle containing a sample to be analyzed on both of a biochemical analysis item and an immune analysis item is sample-pipetted by the nozzle tip first, and then transported so as to be sample-pipetted by the pipette nozzle.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a technology for analyzing a body fluidsample, and particularly relates to a handling method of a body fluidsample and an analysis apparatus using the handling method which cansample the body fluid samples using a plurality of pipetting devices.

2. Description of the Prior Arts

Analysis of body fluid samples such as blood and urine samples frompatients is widely performed in order to diagnose pathologies, andautomated analysis apparatuses are used in hospitals and clinicalexamination rooms.

In order to diagnose the pathologies, examination results obtainable byonly one automatic analyzer are insufficient in most cases. In such acase, it is necessary to collect examination data from a plurality ofanalysis units. Japanese Patent Application Laid-Open Nos. 9-281113 and9-304396 disclose an analysis system which can analyze various kinds ofanalysis items by one system.

These prior arts propose an analysis system in which a plurality ofanalysis units for biochemical analysis are arranged along a sample racktransportation line, and a sample rack from a rack supply unit isdropped in at any one of the analysis units to pipette a sample on thesample rack using a pipette nozzle.

The U.S. Pat. No. 5,470,534 discloses an analysis system in which abiochemical analyzer, an immune analyzer and a nucleic acid analyzer arearranged along a transportation path for a sample bottle so that asingle sample can be measured by each of the analyzers. In this priorart, whether or not the sample should proceed to a second measuringstage is determined depending on an analysis result in a first measuringstage. A biochemical analysis item is analyzed in the first measuringstage, and a sample necessary to proceed to the second measuring stagein order to identify a pathology is analyzed by the immune analyzerand/or the nucleic acid analyzer in the second stage.

On the other hand, in the apparatus automatically analyzing body fluidsamples, many samples are successively pipetted usually using onepipette nozzle. Therefore, there arises a contamination problem of thefollowing samples caused by residue of the preceding sample on thepipette nozzle. A technology in regard to carry-over of this kind isdisclosed, for example, in Japanese Patent Application Laid-Open No.4-169851. In this example, analysis of a biochemical analysis item suchas measurement of components usually contained in blood and analysis ofan immune analysis item such as detecting an antigen or an antibodyutilizing cohesive reaction of latex particles using a row of reactioncontainers formed in a circular shape.

Further, Japanese Patent Application Laid-Open No. 4-169851 points outthat useless consumption of washing solution can be prevented byspending sufficient washing time in washing a reagent pipette nozzleafter pipetting a reagent for an immune analysis item using a washingsolution or by increasing a delivery flow rate of the washing solutionto wash the reagent pipette nozzle, and by spending short washing timein washing a reagent pipette nozzle after pipetting a reagent for abiochemical analysis item or by decreasing a delivery flow rate of thewashing solution to wash the reagent pipette nozzle.

In addition, Japanese Patent Application Laid-Open No. 4-169851 alsopoints out that in a case of a sample pipette nozzle different from thereagent pipette nozzle, useless consumption of washing solution can beprevented by controlling the flow rate of the washing solution.

As an another type to pipette a body fluid sample, it is widely known touse a disposable nozzle tip. For example, U.S. Pat. No. 5,639,425discloses a method comprising the steps of providing a tip holder at aposition within a movable range of a coupling tube which can be coupledto a nozzle tip, transporting a nozzle tip from a tip rack on which manynozzle tips are arranged to the position of the tip holder, thencoupling the nozzle tip with an end portion of the coupling tube on thetip holder, discharging a sample sucked inside the coupled nozzle tipinto a reaction container, and after discharging the sample, removingthe nozzle tip from the coupling tube at a tip detaching station.

Moreover, Japanese Patent Application Laid-Open No. 2-25755 discloses ananalysis apparatus in which a plurality of reaction parts are arrangednear the transportation line for transporting the sample rack, and abypass line and a sample dilution part are disposed between thetransportation line and the respective reaction parts.

This reference discloses further that the plurality of reaction partsare constructed to analyze the sample by a calorimathod, an ionselective electrode method and an immunity method. In this example, thesample rack is moved from the transportation line to the bypass line bya rack changer provided in the transportation line, and a dilution armpippetes the sample from the sample rack on the bypass line to thesample dilution part, and other pippetting arm having a differentconstruction pippetes the sample from the sample dilution part to thereaction part. Furthermore, it is disclosed that it is preferable forthe plurality of the reaction parts to be arranged in a sequence toprevent the mutual contamination between the samples.

3. Discussion of the Prior Arts

Many methods for measuring immune analysis items include an operationfor binding a label substance to solid phase utilizing anantigen-antibody reaction (that is, an immune reaction).

In a case where there are needs to analyze both of an immune analysisitem through such a method and a biochemical analysis item through amethod of measuring an absorbance of a reaction solution produced as aresult of the chemical reaction, or there are needs to analyze a DNAanalysis item and biochemical analysis item, it is convenient forhandling samples that plurality of analysis units are placed in ananalysis system and a single sample bottle is commonly used for each ofthe analysis units.

However in U.S. Pat. No. 5,470,534 in connection with the analysissystems of such a type, there is no description on measures for avoidingthe carry-over between samples.

Furthermore, in Japanese Patent Application Laid-Open No. 9-281113 andJapanese Patent Application Laid-Open No. 9-304396, plurality ofanalysis units are disclosed, however there is no description to arrangeboth of a biochemical analysis unit and a immune analysis unit, or toarrange both of the biochemical analysis unit and a DNA analysis unit.

Japanese Patent Application Laid-Open No. 4-169851 proposes that thecarry-over is avoided only by washing operation using a single pipettenozzle repetitively used for both of a biochemical analysis item and animmune analysis item. However, since there is a limitation in theactually applicable washing time or washing flow rate, it is difficultto eliminate the effect of carry-over on a measured value of an immuneanalysis item in which existence of an extremely small amount of aresidual sample causes a problem.

According to the construction using the disposable nozzle tip describedin U.S. Pat. No. 5,637,425, there is no problem on the effect ofcarry-over between samples since the nozzle tip is exchanged for eachsample. However, since there are the coupling operation and thedetaching operation of the nozzle tip for each sample, the method has adisadvantage in that a sufficient processing capacity can not beattained when a large volume of analysis items such as biochemicalanalysis items must be processed in a short time.

In a analysis apparatus described in Japanese Patent ApplicationLaid-Open No. 2-25755, there is not any difference between theconstruction of the plurality of the reaction parts, and it is intendedto prevent the mutual contamination between the samples only by changingthe arranging sequence of the reaction parts. However, the dilution armand the pippeting arm are commonly used for all of the samplesrepeatedly, therefore, it becomes difficult to avoid the carry-overbetween the samples caused by using these arms.

SUMMARY OF THE INVENTION

Object of the Invention

An object of the present invention is not to be affected by carry-overbetween samples on a measured value of an immune analysis item though arepetitively used pipette nozzle in sample sampling for biochemicalanalysis items is employed.

Another object of the present invention is to provide a method and anapparatus which can prevent deterioration of the processing capacity inregard to biochemical analysis items and can avoid the carry-overbetween samples in regard to immune analysis items in a case where thebiochemical analysis items and the immune analysis items are analyzedusing separate analysis units, respectively.

A further object of the present invention is to make it possible toavoid the carry-over between samples by using both of a pipetting deviceof a type which samples a sample using a repetitively used pipettenozzle and a pipetting device of a type which samples a sample using adisposable nozzle.

A further object of the present invention is to provide a method and anapparatus which can process a specified sample without being affected bythe carry-over between samples when being ordered to analyze both ofanalysis item which should highly avoid the carry-over and analysis itemwhich does not need so much to avoid the carry-over.

A further object of the present invention is to provide an apparatuswhich can select a re-measurement logic and/or analysis channel for there-measurement automatically, before the re-measurement of the sample isperformed according to a measurement result of the sample once measured.

Statement of the Invention

The present invention is characterized by an analysis apparatus in whicha sample is sampled from a single sample bottle to a plurality ofreceiving containers using a plurality of sample pipetting devices, andthe each sample received in each of the receiving containers isanalyzed, wherein the plurality of sample pipetting devices includefirst pipetting devices using a disposable nozzle tip and secondpipetting devices using a repetitive used pipette nozzle, and operationof sampling the sample from the single sample bottle is executed by thesecond pipetting devices after executed by the first pipetting devices.

It is preferable that the analysis apparatus comprises at least twokinds of analysis units, and a first analysis unit has the firstpipetting device using a disposable nozzle tip and a second analysisunit has the second pipetting device using a repetitively used pipettenozzle. In this case, in regard to a specified sample to be analysismeasured in the first and the second analysis unit, sample sampling isexecuted in the first analysis unit in prior to sample sampling in thesecond analysis unit, and the sample sampling in the second analysisunit is executed after completing of sampling the specified sample bythe first analysis unit.

The analysis apparatus comprises a standby unit for letting a samplerack which has been already executed sample sampling in the firstanalysis unit but not yet executed sample sampling in the secondanalysis unit stand by therein (the sample rack has the specifiedsample). The specified sample is transported to the first analysis unitfrom the standby unit to be sampled in the first analysis unit forre-measurement before sampling the specified sample in the secondanalysis unit when a measured result of the first analysis unit inregard to the specified sample is necessary to execute there-measurement.

By constructing in such that the first analysis unit measures an immuneanalysis item or a DNA analysis item, and the second analysis unitmeasures a biochemical analysis item, the immune analysis item or theDNA analysis item is sampled before sampling relating to the biochemicalanalysis item.

In this case, whenever the samples are changed, the nozzle tips arechanged, and the analysis measured value of the immune analysis item orthe DNA analysis item is not affected by the carry-over between samples.

Furthermore, the analysis measured value of the biochemical analysisitem does not receive the affection by the carry-over between samples bywashing the pipette nozzle repetitively used for sampling the samplerelating to the biochemical analysis item by a well-known washing methodwhenever the samples are changed.

In the analysis apparatus, an analysis item which needs to avoid theaffection of very small carry-over between the samples, that is, aspecified analysis item requiring sample sampling by a nozzle tip ispre-registered in the analysis apparatus. Such a specified analysis itemis stored in a memory unit in a control unit, and if the specifiedanalysis item is included among items to be analyzed on many sampleseach of which is instructed by an operator, the sample is transportedinitially to the first analysis unit to be sampled using a nozzle tipbefore it is transported the other analysis apparatus when samplesampling is performed on the sample.

A specified sample rack having a specified sample required to beanalyzed in both of the first and the second analysis unit is restrictedin the transportation order or the transportation path as describedabove, but a sample rack having only samples not required to be sampledby the nozzle tip is transported so as to be let drop in at theplurality of analysis units in arranging order depending on necessity tobe sampled. In this case, the sampling process is efficiently performed.

In a case where the plurality of analysis units include a first analysisunit having a pipetting device using a disposable nozzle tip and asecond and a third analysis apparatus having a pipetting device using arepetitively used pipette nozzle and the plurality of analysis units arearranged at positions in the order of the third analysis apparatus, thefirst analysis unit and the second analysis unit from the side near therack supply unit, in regard to a specified sample rack having aspecified sample necessary for analysis measurement in the first, thesecond and the third analysis apparatus, the specified sample rack beingtransported to the first analysis unit to execute sample sampling usingthe nozzle tip first, then the specified sample rack being let stand byin the standby unit, the specified sample rack on standby in the standbyunit being transferred to the rack transporting apparatus through thereturning line when re-measurement of the specified sample by the firstanalysis unit is determined to be necessary, then sample sampling forthe re-measurement in the first analysis unit being executed.

Then, in the first analysis unit, the specified sample rack having thespecified sample finished sampling of sample for re-measurement istransferred to the rack transporting apparatus through the returningline, and then the specified sample is sampled in the third analysisapparatus and/or the second analysis unit. On the other hand, whenre-measurement of the specified sample is determined to be unnecessary,the specified sample rack on standby in the standby unit is transferredto the rack transporting apparatus through the returning line and thenthe specified sample is sampled in the third analysis apparatus and/orthe second analysis unit.

A method of handling a body fluid sample in accordance with the presentinvention is characterized by that a sample rack having a sample ispositioned to at least one out of a plurality of analysis units, andanalysis of the sample sampled on the sample rack is performed in theanalysis apparatus, wherein the method comprises the steps of processingthe sample by an analyzer having a first analysis unit having a firstpipetting device using a disposable nozzle tip and a second analysisunit having a second pipetting device using a repetitively used pipettenozzle; transporting a specified sample rack having a specified sampleto be analyzed in the first and the second analysis unit to the firstanalysis unit to sample the specified sample in the first analysis unitin prior to transferring the sample rack to the second analysis unit;letting the specified sample rack finished sampling of sample in thefirst analysis unit temporarily stand by in a standby unit beforetransporting the specified sample rack to the second analysis unit;judging whether or not re-measurement of the specified sample by thefirst analysis unit is necessary; transporting the specified sample rackfrom the standby unit to the second analysis unit and sampling thespecified sample by the pipette nozzle if the result of judgment is thatre-measurement of the specified sample by the first analysis unit is notnecessary; transporting the specified sample rack from the standby unitto the first analysis unit and sampling the specified sample forre-measurement in said first analysis unit if the result of judgment isthat re-measurement of the specified sample by the first analysis unitis necessary; and transporting the specified sample rack finishedsampling of the sample for re-measurement to the second analysis unitand sampling the specified sample by the pipette nozzle.

Furthermore, in the handling method of the biochemical sample based onthe present invention, an image plane to for selecting the analysisitems relating to the respective samples is displayed on a displaydevice, and an indication field to indicate a necessity to avoid thecarry-over between the sample relating to the selected analysis item isdisplayed on the display device. When the sample to be analyzed theanalysis item which is indicated to need to avoid the carry-over and theanalysis item which is not indicated to need to avoid the carry-over,are sampled in the analysis part, the sampling relating to the analysisitem which is not indicated to need to avoid the carry-over isperformed, after the sampling relating to the analysis item which isindicated to need to avoid the carry-over finishes.

In this case, the information to show the necessity to avoid thecarry-over is stored in a memory device relating to the analysis itemwhich is indicated the necessity to avoid the carry-over, after that, amemorized information may be output on the display device when the sameanalysis items are selected.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a plane view showing the outline of a configuration of anembodiment in accordance with the present invention.

FIG. 2 is an enlarged plane view showing an analysis unit for the immuneanalysis items of the analysis apparatus shown in FIG. 1.

FIG. 3 is a view for explaining operation of a pipetting device in theanalysis unit shown in FIG. 2.

FIG. 4 is an enlarged perspective view showing an analysis unit for thebiochemical analysis items of the analysis apparatus shown in FIG. 1.

FIG. 5 is a view for explaining a screen for setting a sample volume, areagent volume and a carry-over avoiding level.

FIG. 6 is a view for showing an example of a screen for selecting adesignated analysis item for each sample.

FIG. 7 is a view showing an example of the screen for selecting adesignated analysis item for the same sample as that in FIG. 6.

FIG. 8 is an outline of a configuration of an another embodiment inaccordance with the present invention.

FIG. 9 is an outline of a configuration of the third embodiment inaccordance with the present invention.

FIG. 10 is a view for explaining an operating flow of the analysisapparatus shown in FIG. 9.

FIGS. 11A and 11B respectively are views for showing a process flow fortransporting the sample rack of the analysis apparatus shown in FIG. 9.

FIG. 12 is an outline of a configuration of the fourth embodiment inaccordance with the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

In a preferred embodiment of the present invention, a sample bottlecontaining a body fluid sample such as blood, blood serum or urine ishandled in a state of being held in a sample rack as a bottle holder. Itis preferable that the sample rack can hold one or more sample bottles,but in the following embodiment, an example as that one sample rack canhold up to five sample bottles.

FIG. 1 is a plane view showing the outline of a configuration of anembodiment of an automatic analysis apparatus to which the presentinvention is applied. In FIG. 1, a rack supply unit 10 is operated so asto supply a sample rack 2 to a rack transportation line 60 of a racktransportation apparatus. The rack supply unit 10 comprises an areacapable of placing a tray on which a plurality of sample racks arearranged and an identification read unit 15. The rack supply unit 10 issometimes called as a rack loading unit because the rack supply unit isloaded with the sample rack 2 having samples. The sample racks 2supplied to the rack supply unit are pushed to an entrance side of therack transportation line 60 one-by-one by a well-known rack pushingmechanism. The pushed sample rack 2 is moved up to a reading position ofthe identification read unit 15 by a mover such as a movable hook.

The sample rack 2 is, for example, a rectangular parallelepiped shapedholder, and can hold the plurality of sample bottles 5 (Refer FIG. 2) ina row along the lateral direction of the sample rack. To the sample rack2 of this type, a bar-code label having coded rack identificationinformation including kind of rack and rack number is attached. In eachof the sample bottle 5, a bar-code label having coded sample informationsuch as bottle identification number, patient code, medical sectionnumber, sample receipt number is attached.

The automatic analysis apparatus of FIG. 1 comprises a rack stoker 30orderly storing the sample racks transported by the rack transportationline 60. A electrolyte item analysis unit 300, a immune item or DNA itemanalysis unit 100, a biochemical analysis unit 200 and a standby unit 20as a standby unit are arranged in this order from a position near therack supply apparatus along the rack transportation line 60 between therack supply apparatus 10 and the rack stoker 30.

The electrolyte item analysis unit 300 comprises a pipetting device 302which pipettes a sample from a sample bottle on the sample rack stoppingat a sample pipetting position on the rack transportation line 60 forthe electrolyte item analysis unit 300 to a dilution container 305contained in the electrolyte item analysis unit 300.

The pipetting device 302 has a repetitively used pipette nozzle, thatis, a pippeting nozzle commonly used for the different samples, sucksand holds a sample in a sample container on the sample rack in thepipette nozzle, and discharges a predetermined amount of the held sampleinto the dilution container 305.

The sample diluted with a diluent in the dilution container 305 isconducted to a flow cell by a sucking tube (not shown), and electrolyticcomponents contained in the sample such as sodium ion, potassium ion,chlorine ion and so on are measured using an ion selective electrode foreach ion arranged in the flow cell. An analysis unit control part 301contained in the analysis unit 300 executes calculation to obtain aconcentration of each of the electrolytic components based on a detectedsignal of each ion, and reports the obtained measured value to a totalsystem control unit 50.

The immune item or DNA item analysis unit 100 uses a disposable nozzletip, as to be described later, and comprises a pipetting device 102which is operated so as to suck a sample from a sample bottle on thesample rack positioned at a sample sampling position on a bypass line 61into the nozzle tip, hold the sucked sample in the nozzle tip and thendischarge the preset amount of the held sample into a reaction containeron a reaction disk 103.

The pipetting device 102 exchanges the nozzle tip every time when thesamples are changed. For example, in a case that there is one analysisitem to be analyzed in the analysis unit 100 relating to a formersample, the pipetting device 102 removes the used nozzle tip after onesampling operation is performed for the former sample, and then a newnozzle tip is mounted.

On the other hand, in a case that there is three analysis items to beanalyzed in the analysis unit 100 relating to the following next sample,the pipetting device 102 removes the used nozzle tip after the treetimes of the sampling to the three reaction containers are performed,after that, the new nozzle tip is mounted.

When the analysis unit 100 is that used to analyze the immune analysisitem, the sample pipetted in the reaction container on the reaction disk103 is mixed with a reagent for immune reaction. After immune reactionbetween the sample and the reagent, an analysis item is measured throughfurther steps if necessary. In this case, the word “immune reaction” isa synonym for antigen-antibody reaction.

When the analysis unit 100 is that used to analyze the DNA analysisitem, the sample pippeted in the reaction container on the reaction disk103, is mixed with a reagent for nucleic acid analysis, afterhybridization reaction thereof, a portion combined with a label is cutout with a restriction enzyme, and analysis results of the DNA analysisitems are obtained base on the measurement of the label.

A feature for obtaining a measured value of an immune analysis itemutilizing an immune reaction between a sample and a reagent is a methodof measuring a label substance utilizing a sold phase such as magneticparticles produced by an antibody. For example, a substance to beanalyzed in a sample and a solid phase are bound by a immune reaction,and a reagent having a label substance is bound to the first complex,and then the solid phase is separated from liquid phase. The separatedliquid phase is conducted to a flow cell, and the label substance ismeasured through fluorescence photometry or chemi-luminescencephotometry. Otherwise, the solid phase after liquid separation isintroduced to a photometric position, and a marker bound on the solidphase is measured through a chemi-luminescence method or anelectrochemical luminescence method. An analysis unit control part 101contained in the analysis unit 100 performs control of operation of eachmechanism units in the analysis unit 100 and calculation of measureddata on an analysis item.

The biochmical analysis unit 200 comprises a pipetting device 202 forpipetting a sample using a repetitively used pipette nozzle, as to bedescribed later. The pipetting device 202 is operated so as to suck asample from a sample bottle on the sample rack, which is positioned at asample pipetting position on the bypass line 62 through the racktransportation line 60, into a portion near the end of the pipettenozzle, hold the sucked sample in the pipette nozzle, and then dischargethe preset amount of the held sample into a reaction container on areaction disk 203. A chemical reaction between the sample and a reagentis progressed in the reaction container, and a optical characteristic ofthe produced reaction solution is measured. In this example, thereaction solution is optically measured in a sate that the reactionsolution is contained in the reaction container to obtain a measuredvalue of a biochemical analysis item. An analysis unit control part 201contained in the analysis unit 200 performs control of operation of eachmechanism units in the analysis unit 200 and calculation of measureddata on an analysis item.

In the analysis apparatus of FIG. 1, the rack transportation apparatusfor transporting the sample rack having samples includes the racktransportation line 60, the bypass line 61 for the analysis unit 100 andthe bypass line 62 for the analysis unit 200. Each of the bypass lines61, 62 is formed nearly parallel to the rack transportation line 60, andreceives the sample rack in the upstream side of the bypass line fromthe rack transportation line 60, and the sample rack finishing pipettingof the sample in the downstream side of the bypass line is transfered tothe rack transportation line 60. The sample rack on the racktransportation line 60 and the bypass line 61, 62 is transported to apreset position by a well-known transporting means in which a beltconveyer or a movable hook is driven by a motor.

The sample rack 2 having the sample is positioned in at least one of theplurality of analysis units, and the sample is pipetted from the samplebottle on the sample rack by the corresponding analysis unit, and thenthe sample rack is transported to the standby unit 20. A sample rackhaving possibility of re-examination is let stand by in the standby unit20 until the control unit judges necessity of re-measurement. The samplerack entering into the standby unit 20 is moved along a U-shaped path.The sample rack having no samples judged to be necessary to bere-measured from the measured results of the corresponding analysis unitis immediately contained in a rack stoker 30. However, the sample rackhaving any samples judged to be necessary to be re-measured from themeasured results of the corresponding analysis unit is transferred fromthe standby unit 20 to the returning line 65, transported to theentrance side of the rack transportation line 60 from the returning line65, transferred to the rack transportation line 60 again and transportedto the analysis unit for the re-measurement to be sampled.

As described above, the standby unit 20 lets the sample rack finishedsampling of sample in any one out of the plurality of analysis unitstemporarily stand by therein, but the sample rack finished sampling ofsample in the analysis unit 100 for the immune analysis item isspecially handled. That is, letting a sample instructed to be necessaryfor analysis and measurement by the three analysis units 100, 200, 300or by the two analysis units 100, 200 be called as a specified sample,and letting a sample rack having the specified sample be called as aspecified sample rack, the specified sample rack is initiallytransported to the analysis unit 100 for the immune analysis item tosample the specified sample by a disposable nozzle tip coupled with thepipetting device 102 in prior to transported to the other analysis unit.The specified sample rack is let enter into the standby unit 20 withoutdropping in at any other analysis unit. Then, when it is judged from ameasured result of the analysis unit 100 in regard to the specifiedsample that execution of the re-measurement to the specified sample isnecessary, the specified sample standing-by at the standby unit 20 istransferred to the rack transportation apparatus 60 through thereturning line 65.

The specified sample rack to be re-measured is transported to theanalysis unit 100 for the immune analysis item by the racktransportation apparatus without dropping in at any other analysis unitto be sampled the specified sample for the re-measurement. At that time,a new nozzle tip is coupled to the nozzle coupling tube of the pipettingdevice 102. Such operation is performed only in a case where one samplebottle is held on the sample rack. In a case of a plurality of samples,the transporting operation of the sample rack becomes complex because itis necessary to satisfy sampling of all the samples.

Operations of the rack supply unit 10, the standby unit 20, the rackstoker 30, the transportation apparatus including the transportationline 60 and the returning line 65 are controlled by the total systemcontrol unit 50. A read result by the bar code reader 16 as anidentification information reading unit for the sample rack and thesample bottle is also transmitted to the total system control unit 50.The total system control unit 50 comprises a memory unit 51, andconnected to an operating unit 52 with a key board, a CRT 53 as a screendisplay unit, a printer 54 for output an analysis result of each sample,and a floppy disk memory 55 storing an operating program of the analysisapparatus.

Since an item to be analyzed to each sample on each sample rack ispre-instructed from the operating unit 52 before starting analysisoperation and stored in the memory unit 51, the total system controlunit 50 compares read information by the bar code reader 16 with thestored analysis item information and can be determine an analysis unitto which each sample rack should be transported based on the comparisonresult.

In the example of FIG. 1, one set of the analysis unit 100 used foranalysis measurement of an immune analysis item and one set of theanalysis unit 200 used for analysis measurement of a biochemicalanalysis item are arranged. Two or more sets of these analysis unit foreach may be arranged along the rack transportation line 60.

An example of the construction of the unit for the immune analysis itemwill be described in detail below, referring to FIG. 2 and FIG. 3. Thefirst analysis unit 100 comprises the pipetting device 102 for pipettinga sample, a reaction disk 103 having a constant temperature maintainingfunction and capable of rotationally moving the mounted reactioncontainers 105, a rotatable reagent disk 115 on which reagent bottles117 are arranged along the circumference combining a plural kinds ofreagents for each analysis item, a reagent pipetter 110 for pipetting areagent from the reagent bottle 117 to the reaction container 105 on thereaction disk 103, a sipper mechanism 130 for introducing a mixedsolution of the sample and the reagent formed on the reaction disk 103,an unused reaction container 105 placed in a part supply area 135 and acarriage mechanism 120 for transporting an unused nozzle tip 125 to apredetermined position by a gripper.

The pipetting device 102 for sampling a sample has a coupling tube 104capable of detachably coupling with the disposable nozzle tip 125 shownin FIG. 3. The coupling tube 104 is connected to a pump system 109having a sucking and discharging mechanism, and supported to a movablearm 106 movable in the vertical direction and rotatable in thehorizontal direction.

When analysis operation is started, the transportation mechanism 120grips a disposable unused reaction container 105 placed in the partsupply area 135 by the gripper 128 to transport it to the reaction disk103, and releases gripping at a position 121 to put the reactioncontainer on the reaction disk. Then, the transportation mechanism 120grips the unused nozzle tip 125 placed in the part supply area 135 bythe gripper 128 and releases gripping at a coupling position 107 to putthe nozzle tip on the coupling position.

The sample rack 2 transported from the rack supply unit 10 through racktransportation line 60 is transferred to the bypass line 61 of theanalysis unit 100, and moved to a sample sampling position 111. Thepipetting device 102 positions the movable arm 106 to the couplingposition 107, and moves down the coupling tube 104 to engage the unusednozzle tip 125 with the end of the coupling tube 104 (refer to FIG. 3).Then, the pipetting device 102 rotates the coupling tube 104 to thesampling position, and inserts the end of the nozzle tip 125 up toslightly lower than the liquid surface of the sample in the samplebottle 5 on the sample rack to suck a preset amount of the sample in thenozzle tip 125 and hold it there.

Since the unused reaction container 102 has been moved from the position121 to a discharging position 112, the pipetting device 102 dischargesthe preset amount of the sample held in the nozzle tip 125 to thereaction container 105 placed at the discharging position 112. After thesampling is repeated necessary times relating to the one sample, thepipetting device 102 moves the coupling tube 104 to a detaching position108 to remove the used nozzle tip 125 from the coupling tube 104. Theremoving operation of the nozzle tip is performed by bringing the upperend surface of the nozzle tip in contact with a lower surface of a splitgroove larger than an outer diameter of the coupling tube 104 andsmaller than an outer diameter of the upper end of the nozzle tip 125,and then moving the coupling tube 104 upward. The removed nozzle tip iscollected in a disposal box. In a case where there are a plurality ofanalysis items to be analyzed by the analysis unit 100 on a sample in asingle sample bottle, one nozzle tip is continuously used for samplingthe samples of these analysis items. After that, the nozzle tip isremoved from the coupling tube 104. By doing so, number of consumednozzle tips can be reduced.

The reaction container receiving the sample is moved to a reagentreceiving position 113 by the reaction disk 103. The reagent pipetter110 sucks a dispersed solution of fine magnetic particles as a solidphase into the pipette nozzle at a position 118, and discharges thedispersed solution to the reaction container on the reagent receivingposition 113. Thus, a first immune reaction of binding a substance to beanalyzed in the sample, for example, an antigen to the solid phase isstarted. After a predetermined time, a reagent containing a labelsubstance sucked into the pipette nozzle is discharged from the reagentpipetter 110 at the position 119 into the reaction container againpositioned at the reagent receiving position 113. Thus, a second immunereaction of binding the label substance to the substance to be analyzedin the reaction container is started. The pipette nozzle of the reagentpipetter 110 is used by washing every reagent pipetting.

After that, the reaction container 105 containing the reaction solutionof the immune reaction is positioned at a sucking position 114 by thereaction disk 103. The sipper mechanism 130 introduces the reactionsolution to a detection unit 140 from the reaction container at thesucking position 114 through a sucking nozzle. In the detection unit140, the liquid phase containing substance not binding with the magneticparticles flows through while the magnetic particles are being attachedonto the wall surface by a magnet. By doing so, the solid is separatedfrom the liquid phase. The separated liquid phase is conducted to ameasuring unit to measure fluorescence or chemi-luminescence of thelabel substance contained in the liquid phase. Otherwise, the separatingposition and the measuring unit are commonly used, and measurement isperformed by generating chemi-luminescence orelectro-chemical-luminescence from the label substance binding with themagnetic particles through the substance to be analyzed. After that, thesipper mechanism 130 sucks a washing solution from a washing tank 131through the sucking nozzle to wash the flow passage of the detectionunit 140. The used reaction container is removed from the reaction disk103 by the transportation mechanism at the position 121.

An example of the construction of the analysis unit for the biochemicalanalysis item in FIG. 1 will be described below in detail, referring toFIG. 4. The analysis unit 200 for analyzing a biochemical analysis itemcomprises a reaction disk 203 on which transparent reaction containers205 are concentrically arranged. Water maintained at a presettemperature (for example, 37° C.) is supplied to a constant temperaturebath of the reaction disk 203 from a constant temperature water supplyunit 230. There are two sets of reagent supply systems, and a reagentselected out of many reagent bottles 217 arranged in the first reagentdisk 215 is pipetted to the reaction container 205 on the reaction disk203 by a reagent pipetter 210, and a reagent selected out of manyreagent bottles 218 arranged in the second reagent disk 216 is pipettedto the reaction container 205 on the reaction disk by a reagent pipetter211. A mixer 219 mixes a mixture of the sample and the reagent in thereaction container.

The pipette unit 202 for pipetting a sample comprises a pipette nozzle225 capable of sucking and discharging liquid, and can position thepipette nozzle at a sample pipetting position on the bypass line 62, asample discharging position 204 on the reaction disk 203 and a probewashing tank 207. The pipette nozzle 225 finishing pipetting a sample onthe sample rack 2 is washed in an outer wall surface and an inner wallsurface of the pipette nozzle with a washing solution in the probewashing tank 207 before pipetting another sample, and repetitively usedfor many samples.

A reaction solution between the sample and the reagent formed in thereaction container 205 on the reaction disk 203 is irradiated with alight beam from a multi-wavelength light source 235 in a state ofcontained in the reaction container. The light passed through thereaction container is converted to a spectrum by a multi-wavelengthphotometer 240 to selectively detect a wavelength corresponding to ananalysis item, and the measured light signal is digitized by ananalogue-digital converter 245 and input to an analysis unit controlpart 201 to be calculation processed. The reaction container finishingphotometrical measuring is washed in a container washing unit (notshown) and moved to the sample discharging position so as to receive anew sample.

In the analysis unit 200 of FIG. 4, the sample rack 2 transferred to thebypass line 62 through the rack transportation line 60 is positioned atthe sample sampling position on the bypass line 62. The pipetting device202 inserts the end of the pipette nozzle 225 up to slightly lower thanthe liquid surface of the sample in the sample bottle 5 at the samplepipetting position and sucks a preset amount of the sample in to aportion near the end of the probe and hold it there, and then moves thepipette nozzle 225 to the sample discharging position 204 of the row ofthe reaction containers. After that, the sample held in the probe isdischarged into a washed reactor container placed at the dischargeposition 204.

The reaction container 205 receiving the sample is moved to a firstreagent adding position by the reaction disk 203, and the first reagentcorresponding to the analysis item is pipetted into the reactioncontainer by the reagent pipetter 210. Then, the mixture in the reactioncontainer is mixed by the mixing mechanism 219 to progress the chemicalreaction between the sample and the reagent. In a case of an analysisitem requiring a second reagent, the second reagent is further added tothe reaction container at a second reagent adding position by thereagent pipetter 211. The reaction container containing the reactionsolution is moved so as to cross a light beam of a photometricalposition 241, and an absorbance of the reaction solution is measuredbased on the transmitting light at that time, and a concentration of thesubstance to be measured or an enzyme active value in the sample iscalculated by the analysis unit control part 201 and the measured resultis stored in the memory unit 51 of the total system control unit 50.

An example of operation of the automatic analysis apparatus in theembodiment of FIG. 1 will be described below, referring to FIG. 5 toFIG. 7. Before starting analysis operation, analysis items required foreach sample from a patient are input through the operating unit 52. Eachof the sample is usually requested to perform analytical examination ona plurality of analysis items. In the automatic analysis apparatus, ananalysis item having a high necessity to avoid the carry-over is presetand stored in the memory unit 51 of the total system control unit 50.

When setting of analysis condition is instructed from the operating unit52, an analysis condition setting screen 70 is displayed on the CRT 53as a screen display unit. This screen 70 comprises a button 71 forinvoking a routine operation screen, a button 72 for invoking a reagentcontrol screen, a button 73 for invoking a calibration screen, a button74 for invoking an quality control screen, and a button 75 for invokinga utility screen arranged in an upper section, as shown in FIG. 5. Bytouching each of the buttons with a finger by a touching panel method,or by clicking each of the buttons with a pointer by operating a mouse,the corresponding screen is displayed in the central portion. FIG. 5shows an example of invoking a corresponding screen by touching theutility screen invoking button 75. A help button 76 is arranged belowthe analysis condition setting screen 70, and by touching this button 76an explanation sentence for screen operation is displayed.

A button 81 for instructing stopping the analysis apparatus, a button 82for instructing stopping sampling operation during analysis operation, abutton 83 for invoking an alarm screen, a button 84 for invoking ascreen showing states of each analysis unit and rack transportation, abutton 85 for instructing printing to the printer 54, a button 86 forinstructing starting the analysis apparatus are arranged in an area inthe right hand side or the left hand side of the analysis conditionsetting screen 70. Each of the above-mentioned buttons is alwaysdisplayed when the analysis condition setting screen 70 is displayed.

Here, when the utility screen invoking button 75 is selected, screeninvoking buttons for system 151, maintenance 152, application 153,calculation item 154, carry-over 155, report 156 and unit configuration157 appear in a display area 150, and a button 161 for instructingadding, a button 162 for instructing writing of data base to a floppydisk memory, a button 163 for instructing deleting and a button 164 forinstructing reading from the floppy disk memory appear. When the button153 for invoking an application screen is selected in this state, atable of list 170 showing a plurality of analysis items and sample kindsappears, and detailed screen invoking buttons 171 to 174 appear.

When the analysis button 171 out of the detailed screen invoking buttonsis further selected, a screen shown in FIG. 5 appears in a display area180. That is, a section 181 for setting an amount of sample, a section182 for setting an amount of pipetted reagent, a level setting section183 for setting a carry-over avoiding level and a button 184 forinstructing storing are displayed.

In the analysis items displayed in the table of list 170 in the screenof FIG. 5, TSH means thyrotropin, T4 means thyroxine, TF4 means freethyroxine, CEA means carcino-embryonic antigen, HCG means humanchorionic gonadotropin, TNT means troponin T, HBsAg means hepatitis Bsurface antigen, and a-HBs means hepatitis B surface antibody. All ofthese are immune analysis items.

Here, it is assumed that HBsAg out of the analysis items in the table oflist 170 is selected, and 30 μl of sampling amount of sample is input tothe sample amount setting section 181, and 70 μl of adding amount of thefirst reagent R1, 60 μl of adding amount of the second reagent R2 and 40μl of adding amount of beads reagent are input to the reagent pipetteamount setting section 182. It is also assumed that in the carry-overavoiding level setting section 183, a level “High” is selected between“High” and “Low”. The level selection of high and low can be performedusing a level selection button 187. Then, when the storing instructionbutton 184 is selected, the sample amount and the reagent pipettingamounts in regard to the analysis item of HBsAg and the avoiding levelof carry-over between samples corresponding to the analysis item areinstructed, and stored in: the memory unit 51.

Then, by selecting another analysis item displayed in the table of list170 and similarly setting a sample volume, a reagent pipetting volumeand a carry-over avoiding level corresponding to the item, theseconditions can be successively set. On the other hand, by constructingso that a plurality of analysis items are selected and a commoncarry-over avoiding level may be instructed, the carry-over avoidinglevel can be instructed to the plurality of analysis items at once.

The level “High” in the carry-over avoiding level setting section 183 isfor performing sample sampling under a condition of no carry-overbetween samples and, in more detail, the total system control unit 50controls a transporting destination of a corresponding sample rack so asto perform sampling of the sample by a pipetting device using thedisposable nozzle tip to be exchanged by a new one for each sample. In acase where the “High” level is instructed on a specified analysis item,the memory unit 51 stores the specified analysis item requiringpipetting using a disposable nozzle tip. On the other hand, the level“Low” is an instruction that sampling of the sample may be performed bya pipetting device having the pipette nozzle repetitively used for manysamples by washing it, and an analysis item corresponding to this casecan be analyzed in the analysis unit 200 and/or the analysis unit 300 inFIG. 1.

The analysis condition set through the setting screen as shown in FIG. 5is continuously used corresponding to each analysis item unless thecondition is changed after that. Therefore, when an examination of apatient sample is requested, the analysis condition set in FIG. 5 isautomatically applied if an analysis item to be described later isinput.

In this way, in the analysis apparatus shown in FIG. 1, a special methodto avoid the carry-over between the samples, is needed, that is, whenthe analysis item is indicated as being in a level of “high”, anindicated information thereof as being in a level of “high” is stored ina memory device. After that, when the same analysis item with that whichis already indicated in order to set a new analysis condition, isselected by referring the analysis condition setting screen 70, thestored information, that is, the information having a necessity to avoidthe carry-over operates so as to be output on the display device. In thecase shown by FIG. 5, when the analysis item is selected, information“high” is displayed on the level setting section.

An operator work at starting routine analysis work will be describedbelow. By selecting the button 71 for invoking a routine operatingscreen in the analysis condition setting screen 70, an item selectingscreen as shown in FIG. 6 is displayed in the large display area 150 onthe CRT 53. A section 251 for selecting a sample kind, a section 252 forinputting a sample number, a section 253 for inputting a patientidentification number, a section 254 for selecting a kind of sample cup,an area 255 for selecting an analysis item, a button 256 for instructinga preceding sample, a button 257 for instructing a following sample anda button 258 for instructing registering are displayed in this screen.The analysis item selecting area 255 among these has a reservationregistering function of 5-page capacity, and each of the pages has 24item inputting sections or analysis item selecting sections. When thepreceding sample instructing button 256 is selected, analysis iteminformation on a sample preceding a sample displayed at present by oneis displayed instead of the contents displayed at present. When thefollowing sample instructing button 257 is selected, analysis iteminformation on a sample following a sample displayed at present by oneis displayed.

Therein, the screen of FIG. 6 shows analysis items selected by the firstpage of the analysis item selecting area 255. In the displayed analysisitems, AST means asparatate aminotransferase, ATL means alanineaminotransferase, IP means inorganic phosphorus, TP means total protein,Alb means albmin, LD means lactate dehydrogenase, UA means uric acid,CRE means creatinine, Na means sodium ion, and K means potassium ion.

FIG. 6 is an example of selecting 10 items of biochemical analysis itemsto be analyzed in the first page in regard to a blood serum sample ofsample number 1. FIG. 7 is an example of selecting 7 items of immuneanalysis items to be analyzed in the second page in regard to the bloodserum sample of the same sample number. By selecting the registrationinstructing button 258 after finishing inputting all the analysis itemsrequested to examine on the single sample, analysis measurement of theplurality of analysis items on the sample is reserved and stored in thememory unit 51. Since the screen of the display area 150 is updated bythis registering operation, analysis item selection on a sample of thenext sample number can be performed. Thus, the operator can successivelyperform analysis item selecting work on all the requested samples. Inthe example of FIG. 6 and FIG. 7, 17 analysis items on the sample ofsample number 1 are registered as a result.

By selecting the reagent control screen invoking button 72 of theanalysis condition setting screen, the screen for setting analysis itemsto be analyzed and measured to each of the analysis units in theanalysis apparatus of FIG. 1 is displayed. Such allocation of analysisitems to each of the analysis units is performed in prior to theinputting work of requested analysis items for each sample as shown inFIG. 6. When a process of which analysis item is allocated to whichanalysis units, the carry-over avoiding level between samples set inFIG. 5 is reflected. That is, an analysis item of “High” level isallocated to the analysis unit 100 having the pipetting device using thedisposable nozzle tip.

On the other hand, when items to be analyzed are instructed for eachsample in routine work, the relationship between analysis item andcarry-over avoiding level and the analysis items allocated to eachanalysis unit are already registered in the control unit of theautomatic analysis apparatus. Therefore the control unit checks arequested analysis item, for example, on a sample of sample number 1,and judges which analysis unit among the plurality of analysis units thesample is analyzed in. For example, since the sample of sample number 1is relates to the analysis unit 300 in its electrolytic component, tothe analysis unit 100 in its immune analysis item and to the analysisunit 200 in its biochemical analysis item, in the example of theconstruction of FIG. 1 the sample is analyzed in all the analysis units.

In the cases that the analysis conditions for the respective analysisitems are set by using the screens shown in FIGS. 5 to 7, the screenwhich is used to select the analysis item to be set the analysiscondition, is displayed on the display device, and the indication fieldto be able to indicate the necessity to avoid affection of thecarry-over between the samples corresponding to the analysis itemselected on the screen, is displayed on the display device.

After that, when the samples to be analyzed the analysis items which isindicated the necessity to avoid the carry-over and which is notindicated the necessity to avoid the carry-over through the displaydevice, are sampled in the analysis part such as the analysis units 100,200, 300 etc., the sampling of the sample relating to the analysis itemnot indicated the necessity is executed after the sampling of the samplerelating to the analysis item indicated the necessity is executed.

An example of handling a sample in the automatic analysis apparatus ofFIG. 1 will be described below. For the purpose of convenience, it isassumed that a single sample analyzed on an electrolytic substanceanalysis item and a biochemical analysis item is held on the firstsample rack firstly supplied from the rack supply unit 10 to the racktransportation line 60, and a single sample analyzed on an electrolyticsubstance analysis item, a an immune analysis item and a biochemicalanalysis item is held on the second sample rack secondarily supplied. Ina case where a plurality of samples are held on a single sample rack,the transportation rout of the sample rack is determined so that samplesampling of analysis items relating to all the samples is performed.

The first sample rack pushed out from the rack supply unit 10 to thetransportation apparatus side is positioned at the reading position ofthe identification reading unit 15, and the bar code label of sampleinformation attached to the sample bottle is read by the bar code reader16. The total system control unit 50 determines analysis unit at whichthe first sample rack should drop in by comparing the read informationwith analysis information instructed to the samples, and recognizingbased on the compared result that there is no specified analysis itemrequiring sampling by the nozzle tip, and recognizing requested analysisitems corresponding to analysis items allocated to each of the analysisunits.

Since the first sample rack has no samples requiring analysis by theanalysis unit 100 for the immune analysis item, the total system controlunit determines that the first sample rack is transported so as to dropin at the analysis unit 300 for the electrolytic analysis item placed inthe position near the rack supply unit 10, and then drop in at theanalysis unit 200 for the biochemical analysis item. That is, the sampleracks in this case, are transported to the plurality of the analysisunits according to the arranging order thereof and depending on thenecessity. Both of the second analysis unit 200 and the third analysisunit 300 are analysis units having the pipetting device using therepetitively used pipette nozzle.

The first sample rack of which the identification information has beenread is moved to the sample sampling position of the analysis-unit 300for the electrolytic analysis item, and the pipetting device 302 sucks apart of the sample on the sample rack and discharge it to the dilutingcontainer 305 as a receiving container. The first sample rack finishingsample sampling at the analysis apparatus 300 is transported to theanalysis unit 200 for the biochemical analysis item without dropping inat the analysis unit for the immune analysis item.

The first sample rack is once stopped at the entrance of the bypass line62 and then transferred to the bypass line 62, and positioned at thesample sampling position on the bypass line 62. The pipetting device 202repeats operation of pipetting the sample in the sample bottle on thefirst sample rack to a plurality of reaction containers 205 number ofwhich is corresponds to number of items to be analyzed. After finishingsample sampling for a predetermined number of analysis items, the firstsample rack is transferred to the rack transportation line 60, and thentransported to the standby unit 20.

If the control unit judges that the analysis result by each of theanalysis apparatus does not require any re-measurement, the first samplerack goes out of the standby unit 20 and is stored in the rack stoker30. If the control unit judges that the analysis results by the analysisunit requires re-measurement on one or more analysis items, the firstsample rack on standby in the standby unit 20 is transferred to thereturning line 65 to transported to the entrance side of the racktransportation line 60, and then transported to the analysis unit 200again by the transportation line 60. After plural times of samplesampling corresponding to number of analysis items for re-measurement,the first sample rack is stored in the rack stoker 30 through thetransportation line 60. The analysis results in regard to the sample onthe first sample rack by the units 200, 300 may be output to the CRT 53and the printer 54.

While the first sample rack is under processing, the second sample rackmay be supplied from the rack supply unit 10 to the entrance side of therack transportation apparatus. The second sample rack is moved to thereading position of the identification reading unit 15, and the sampleinformation expressed by the bar code on the outer wall of the samplebottle is read by the bar code reader 16. The control unit determinesanalysis unit at which the second sample rack should drop in by checkingthe analysis condition set information and the instructed informationinput or selected by the operating unit 52 and the read information inregard to the sample on the second sample rack. Since the body liquidsample held on the second sample rack is instructed so as to be analyzedon an electrolytic analysis item, an immune analysis item and abiochemical analysis item, it is determined that the second sample rackdrops in the analysis units 100, 200 and 300 in the construction exampleof FIG. 1.

In this case, the control unit recognizes that the specified analysisitem requiring pipetting by the disposable nozzle tip is included amongthe plurality of analysis items instructed to perform analysis, anddetermines that the second sample rack is transported firstly to theanalysis unit 100 which can perform such pipetting. Based on thedetermination, the control unit controls operation of the racktransportation apparatus so that the second rack is transported to theanalysis unit 100 in prior to transporting to the other analysis units.An analysis item allocated to the first analysis unit is not limited toan immune analysis item, but an analysis item set to “High” in thecarry-over avoiding level between samples as shown in FIG. 5 may beallocated to the analysis unit 100 even if it is a biochemical analysisitem.

Based on the above-mentioned determination of the transportation order,the second sample rack in the identification reading unit 15 istransported to the bypass line 61 corresponding to the analysis unit 100arranged in the second order through the rack transportation line 60without dropping in at the analysis unit 300 which is the closest to therack supply unit, and positioned at the sample sampling position on thebypass line 61. The pipetting device 102 couples the unused disposablenozzle tip 125 with the coupling tube 104, and repeats operation ofpipetting the sample in the sample bottle on the second sample rack to aplurality of reaction containers 105 number of which is corresponds tonumber of items to be analyzed. The second sample rack after finishingsampling is transferred from the bypass line 61 to the racktransportation line 60, and then transported to the standby unit 20without dropping the analysis unit 200 arranged in the third order.

While the second sample rack is temporally standing by at the standbyunit 20, analysis measured results of the sample by the analysis unit100 can be obtained. Based on the analysis measured results by theanalysis unit 100, the control unit judges necessity of re-measurementon each of the measured analysis items is necessary. If the judgedresult is that re-measurement is unnecessary to any analysis items, thesecond sample rack on standby in the standby unit 20 is transferred tothe returning line 65, and transported to the entrance side of the racktransportation line 60 by the returning line 65. Then, the second samplerack drops in at the analysis unit 300 for the electrolytic analysisitem, and the pipetting device 302 pipettes the specified sample usingthe pipette nozzle. After that, the second sample rack is transported tothe analysis unit 200 arranged in the third order without dropping in atthe analysis unit 100, and positioned at the sample sampling position onthe bypass line 62, and the pipetting device 202 pipettes the specifiedsample using the pipette nozzle 225.

The second sample rack finishing pipetting in the analysis unit 300 andthe analysis unit 200 is transported to the standby unit 20 totemporally stand by at there. Then, necessity of re-measurement isjudged based on the analysis measured results by the analysis units 200and/or the analysis units 300. If re-measurement is unnecessary, thesecond sample rack is stored in the rack stoker 30. If re-measurement isnecessary, the second sample rack is transported to the third analysisunit 300 and/or the second analysis unit 200 again to be sampled for there-measurement. After that, the second sample rack is transported to andstored in the rack stoker 30.

On the other hand, when based on the analysis measured result by theanalysis unit 100 for the immune analysis item, it is judged thatre-measurement on any of the analysis items is necessary, the controlunit transports the second sample rack as follows. That is, The secondsample rack holding a specified sample is transferred from the standbyunit 20 to the returning line 65, and transported to the entrance sideof the rack transportation line 60 by the returning line 65, and thentransferred to the rack transportation line. The rack transportationline 60 transports the second sample rack to the bypass line 61corresponding to the analysis unit 100 without dropping in at theanalysis unit 300. At this time point, sample sampling of the secondsample rack is not performed by the other analysis units 200 and 300yet.

The pipetting device 102 of the analysis unit 100 pipettes the specifiedsample on the second sample rack positioned at the sample samplingposition on the bypass line to the reaction container 105 on thereaction disk 103 using a new disposable nozzle tip in order to measurethe analysis item which is judged that re-measurement is necessary.

The second sample rack finishing sample sampling for re-measurement isonce transferred to the rack transportation line 60, and immediatelytransported to bypass line 62 corresponding to the analysis unit 200.Then, the first sample sampling of the second sample rack by the pipettenozzle 225 of the pipetting device 202 is performed. The second samplerack finishing sample sampling in regard to the specified sample istransferred to the returning line 65 through the rack transportationline 60, and then transferred to the rack transportation line 60 to betransported to the third analysis unit 300. After that, the first samplesampling in regard to the specified sample by the pipette nozzle of thepipetting device 302 is performed.

Otherwise, it is possible to control so that when sample sampling forre-measurement in regard to the analysis unit 100 is finished, thesecond sample rack is transferred to the rack transportation line 60,successively transferred to the returning line 65, transported from theentrance side of the rack transportation line 60, and sample sampling isperformed in the analysis unit 300 and then in the analysis unit 200 inregard to the specified samples, respectively. In any case, the secondsample rack finishing sample sampling in the analysis units 200 and 300is transported to the standby unit 20 to temporally stand by at thereuntil the judgment on necessity of the re-measurement is output. Thetransporting operation in regard to the second sample rack afterjudgment on necessity of the re-measurement is the same as thatdescribed above.

Depending on a patient sample, there is a case where analysis by onlyone analysis unit out of the three analysis units shown in FIG. 1,analyses by the two analysis units for the immune analysis item and thebiochemical analysis item, or analysis by the two analysis units for theimmune analysis item and the electrolyte analysis item is performed. Ina case where a sample is analyzed by the analysis unit 100 and theanalysis unit 200 or 300, the system is constructed so that the sampleis initially sampled in the analysis unit 100, then the sample samplingfor re-measurement is performed in the analysis unit 100, and thensampling operation of the sample in the same sample bottle is performedin the other analysis unit 200 or 300.

As described above, in the embodiment of the apparatus of FIG. 1, sincesample sampling is performed in the analysis unit having the pipettingdevice using the disposable nozzle tip and then sample sampling isperformed in the analysis unit having the pipetting device using therepetitively used pipette nozzle by washing, an analysis item which muststrictly avoid an effect of carry-over between samples can be analyzedwith keeping high reliability. Further, since an analysis item which isnot so strongly affected by an effect of carry-over between samples issampled by the pipetting device using the repetitively used pipettenozzle, the total processing capacity of the analysis apparatus is notreduced so much. Because number of analysis items using the pipettenozzle is much larger than number of items necessary to use thedisposable nozzle tip.

Another embodiment of the construction of an analysis apparatus inaccordance with the present invention will be described below, referringto FIG. 8. The automatic analysis apparatus for analyzing body fluidsamples of FIG. 8 comprises a sample bottle transportation apparatus800, a first analysis unit 810 for analyzing the immune analysis itemand a second analysis unit 820 for analyzing the biochemical analysisitem. The sample bottle transportation apparatus 800 has a rotatablesample disk 801 capable of holding many sample bottles 802 in circularshape.

A first pipetting device 830 is a pipetting device using a disposablenozzle tip by exchanging it for each sample. A second pipetting device840 is a pipetting device using a repetitively used pipette nozzle bywashing. The first analysis unit 810 has a reaction container exchangeapparatus 813 for exchanging a used reaction container with a unusedreaction container and capable of exchangeably arranging many reactioncontainers 812 on a reaction disk 811. A necessary reagent correspondingto an immune analysis item is pipetted from a reagent supply unit 816into the reaction container 812 on the reaction disk 811.

The first pipetting device 830 can couples the unused disposable nozzletip to a tip coupling tube on a tip supplier 814. The used nozzle tip isremoved from the coupling tube to be disposed to a disposal box 815. Thefirst analysis unit 810 has a measuring unit 815 for measuring areaction solution or a solid phase after immune reaction. A reactiondisk 821 in the second analysis unit 820 has a row of transparentreaction containers 822. A necessary reagent corresponding to abiochemical analysis item is pipetted from a reagent supplier 826 tothese reaction containers 822. The second analysis unit 820 has ameasuring unit for measuring an optical characteristic of a reactionsolution after chemical reaction.

In the automatic analysis apparatus of FIG. 8, it is assumed that aspecified sample requiring to be analyzed on both of an immune analysisitem and a biochemical analysis item is contained in one specifiedsample bottle 802. When analysis is started for such a specified sample,the corresponding specified sample bottle is positioned at a samplesampling position by the sample disk 801. Then, the first pipettingdevice 830 coupled with the unused nozzle tip sucks a part of thespecified sample into the nozzle tip and discharges it into the reactioncontainer 812 on the reaction disk 811. An immune reaction between thesample and the reagent is progressed in the reaction container, and thenan immune analysis item to be analyzed is measured.

The automatic analysis apparatus is programmed so that after finishingsample sampling to the above-mentioned specified sample bottle using thefirst pipetting device, the same sample bottle is positioned at a samplesampling position b, and sample sampling using the second pipettingdevice 840 is performed. The specified sample pipetted to the reactioncontainer 822 on the reaction disk 821 by the pipette nozzle of thesecond pipetting device is chemically reacted with the reagent in thereaction container, and the biochemical analysis item is measured basedon photometrical measurement of the produced reaction solution.

Both of a biochemical analysis item and an immune analysis item can bealso measured by the embodiment of FIG. 8, and the analysis measuredvalue of the immune analysis item is not affected by the effect ofcarry-over between samples.

In a case of measuring a biochemical analysis item and an immuneanalysis item, the pipetting device using the disposable nozzle tip andthe pipetting device using the repetitively used pipette nozzle areapplied to a single sample bottle, and pipetting operation by thedisposable nozzle tip is performed in prior to using the pipette nozzle.By doing so, the carry-over between samples caused by the pipette nozzleis avoided relating to the analysis item which should be extremelyavoided, and the pipette nozzle used commonly can be used for samplingthe sample relating to the biochemical analysis item.

Furthermore, the functions as shown in FIGS. 5 to 7 are performed in theembodiment shown in FIG. 8. In this case, the sampling processing effectbecomes lower than that of the embodiment shown in FIG. 1. The controlpart controls respective mechanism of the analysis apparatus. In theanalysis apparatus shown in FIG. 8, when the re-measurement is directedto be executed according to the measurement effect of the sample by theimmune analysis unit 810, it is controlled that the sampling of the samesample is not performed by the second pipetting device 840 at thesampling position b until the first measurement result is obtainedrelating to the specified sample at the position a.

When the re-measurement is judged to need to be done, the correspondingspecified sample is returned to the sampling position a by the sampledisk 801, is sampled again by the first pipetting device 830, and isanalyzed again by the immune analysis unit 810.

After this second time sampling, the corresponding sample is moved tothe sampling position b, and is sampled by the second pipetting device840.

FIG. 9 shows an outline of a configuration of the third embodiment basedon the present invention. The same functions of the elements in thisembodiment as that in the former embodiment are shown by attaching thesame reference numerals.

In FIG. 9, the analysis units 100A, 100B for measuring the immuneanalysis item and the analysis units 200A, 200B for measuring thebiochemical analysis item are arranged along the rack transportationline 60. These analysis units are connected to be able to bedisconnected to the rack transportation line 60.

The sample rack 2 supplied from the rack supply unit 10 can selectivelydrop in at the necessary analysis unit through the bypass lines 61A,61B, 62A, 62B attached on the respective analysis units. The respectiveanalysis units build in respective computers 101A, 101B, 201A, 201B asthe analysis unit control parts.

The computer 11 built in the rack supply unit 10 performs necessarycontrol of the rack supply unit 10, the rack transportation line 60, thereturning line 65, and the rack stoker 30. The computer 21 built in thestandby unit 20 performs necessary control in the standby unit 20. Thesecomputer and the bar code reader 16 are connected to computer 50 as theintegrated controller. The computer 50 gives the necessary informationto the computer 11 and the computer of the analysis unit which is planedto be dropped in by reading out the sample ID and the rack ID.

When the sample held by the sample rack is a sample which is specifiedto perform automatic re-examination and has an immune analysis itemspecified to perform automatic re-examination, after finishing thesampling for immune analysis, the sample rack is transported to thestandby unit 20 by the transportation line 3 to be temporarily let standby. During that period, the computer 50 judges based on a presetalgorithm or logic whether or not re-examination is necessary. If thejudged result is that the re-examination is necessary, the sample rackis returned to the entrance side of the rack transportation line 60 bythe returning line 65. The sample rack is further transported to thesuitable analysis unit by the rack transportation line 60, and thesample held by the sample rack is re-sampled and re-examined, that is,the immune analysis is performed on the sample again. After finishingsampling of the sample for the re-examination of immune analysis in theanalysis unit, the sample rack is transported to the biochemicalanalysis unit and the sample is sampled to perform biochemical analysis.Then, the sample rack is transported to the rack stoker 30 by the racktransportation line 60 to be collected there without dropping in at theother analysis unit nor the standby unit 20 when the sample held by thesample rack is not specified to perform re-examination.

The analysis units 100A, 100B have the same construction with that ofthe analysis unit 100 shown in FIG. 1, and the analysis units 200A, 200Bhave the same construction with that of the analysis unit 200 shown inFIG. 1.

FIG. 10 is a flow chart of the system operation of an automatic analysisapparatus in accordance with the present invention. An operatorinitially sets reagents at preset positions in each analysis unit, andinformation which analysis unit each reagent exists in and whichanalysis item each reagent is to be used for is stored and registered ina memory unit in the computer 50 (S401). The registration may beperformed by operating the operating unit 18 by the operator, or byautomatically reading a-reagent ID having each of the reagent bottles217, 218.

Next, the operator operates the operating unit 52 to specify whether ornot the automatic re-examination logic function is put in action andwhich re-examination logic is put in action if re-examination logic isput in action (S402). This is for automatically performingre-examination only on an analysis item which really requiresre-examination, and largely contributes to suppress decrease inprocessing capacity of the whole apparatus. In detail, the automaticre-examination logic is a logic showing, for example, the followingconditions. The conditions are pre-stored and pre-registered in thememory unit 51 of the computer 50, and the operator can select one bydesignating any one condition, and the designation of the re-examinationof the corresponding analysis item can be cancelled. The automaticre-examination logic is selected through the screen of the CRT 53.

(1) The automatic re-measurement is always performed without anycondition.

(2) The automatic re-measurement is performed when an analysis resultdeparts from an analysis (measurement) range preset for each analysisitem. For example, in regard to TSH (thyrotropin:thyroid-stimulatinghormone), when a first analysis result is above 0.27 IU/ml, but departsfrom a condition below 4.2 IU/ml, the re-measurement is performed.

(3) The automatic re-measurement is performed when a difference betweenan analysis value in this time and an analysis value in the precedingtime (or an analysis value before the preceding time) on samples from asingle person exceeds a preset limit value (for example, when theanalysis value in this time differs from the analysis value in thepreceding time by 50% or more).

After that, the operator operates the operating unit 52 to specify ananalysis (measurement) channel using algorithm when the re-examinationis performed relating to the analysis item (S403). In detail, theanalysis channel using algorithm is a algorithm showing, for example,the following conditions. The conditions are pre-stored andpre-registered in the memory part 51 of the computer 50, and theoperator can be specify and select one condition. The one analysischannel means a combination of one reaction line and one sensor.

(1) The same analysis (measurement) channel as an analysis channel usedfor the analysis (measurement) in the time before the re-examination isused.

(2) An analysis channel different from an analysis channel used for theanalysis in the time before the re-examination is used. This conditionis effective when the analysis channel used in the time before there-examination is abnormal.

(3) A plurality of analysis channels including the same analysis channelused for the analysis in the time before the re-examination are used.This condition is effective when a highly reliable analysis result isattempted to be obtained.

(4) A plurality of analysis channels excluding the same analysis channelused for the analysis in the time before the re-examination are used.This condition is effective when the analysis channel used in the timebefore the re-examination is abnormal and a highly reliable analysisresult is attempted to be obtained.

Although each of the analysis units in the FIG. 1 and FIG. 9 has onlyone analysis (measuring) channel, each of the analysis units may have aplurality of analysis channels. The plurality of analysis channels inthe above items (3) and (4) may have a plurality of analysis channels inone analysis unit, or may have a plurality of analysis channelsextending over a plurality of analysis units within a same immuneanalysis.

The automatic re-examination logic information and the analysis channelusing algorithm may be stored and registered not in the memory part 51in the computer 50 but in a memory unit 55 provided in the external.

Then, after the registration, the operator loading the sample rack tothe sample rack loading unit 1, and operates the operating unit 52 toregister to the computer 50 which sample is analyzed on which analysisitem, that is, register analysis item request (S404). Successively, theoperator operates the operating unit 52 to specify for each samplewhether or not the automatic re-examination logic described above isexecuted by using the screen of the CRT 53 (S405). This is effective fora small amount of an important sample in that the unnecessaryconsumption of the important sample can be prevented by omitting theautomatic re-examination. After finishing the above-mentioned operationsby the operator, analysis operation is started (S406), and a result ofthe analysis is output (S407), and thus the analysis is completed(S408).

FIGS. 11A and 11B are flow-charts of sample rack transportationprocessing in accordance with the present invention. A sample rack isloaded in the rack supply unit 10 (S501). When the loaded sample rack istransported to the rack transportation line 60 (S502), the sample ID andthe rack ID are read by the ID reading unit 16 (S503) and theinformation is transmitted to the computer 50.

The computer 50 judges whether or not there is a sample requested toanalyze on an immune analysis item on the rack (S504). If the result is“YES”, the sample rack is transported to a specified immune analysisunit by the rack transportation line 60 based on a command from thecomputer 50 to the computer 11 (S505). The sample sampling is performedbased on a command from the computer 50 to the computer of the immuneanalysis unit, and immune analysis is performed on the immune analysisitem (S506).

After finishing the sampling, the computer 50 judges whether or not thesampled sample is a sample specified automatic re-examination in StepS405 of FIG. 10 (S507). If the result is “YES”, the computer 11 judgeswhether or not the immune analysis item specified in Step S405 of FIG.10 to perform automatic re-examination is included in the sample (S508).If the result is “YES”, the rack is transported to the sample rackstandby unit 9 by the rack transportation line 60 based on a commandfrom the computer 50 to the computer 11 (S509) and the rack stands bythere until the analysis result is output (S510).

After outputting the result of the above analysis, the computer 50judges based on the re-examination logic specified in Step S402 of FIG.10 whether or not re-examination is necessary (S511). If the result is“YES”, the sample rack is transported to an specified immune analysisunit by the returning line 65 and the rack transportation line 60according to the selected analysis channel using algorithm based on acommand from the computer 50 to the computer 11 (S512).

Pipetting is performed based on a command from the computer 50 to thecomputer of the analysis unit (S513), and thus, the immune analysis iscompleted (S514).

If the judged result in Step S507, S508 or S511 is “NO”, the flowproceeds to Step S514.

After finishing Step S514 or if the judged result in Step S504 is “NO”,Steps S515 to S525 of biochemical analysis corresponding to Steps S504to S514 of immune analysis are similarly performed, respectively. Afterfinishing the analysis or when the analysis is necessary, the samplerack is collected to the rack stoker 30 (S526).

FIG. 12 shows an example of a partial arrangement of another embodimentof an automatic analysis apparatus in accordance with the presentinvention. This embodiment is different from the embodiment of FIGS. 1and 9 in the point that each analysis unit does not have any siding(by-pass line) as shown in FIGS. 1 and 9. Therefore, in this embodiment,the sample rack is kept on the rack transportation line 60 even duringsample sampling.

In the analysis apparatus shown in FIG. 12, at respective lower flowside of the analysis units 100 a, 100B, 200A, 200B, the standby units20A, 20B, 20C, 20D are arranged corresponding to the respective analysisunits. The movement of the sample rack transmitted to the standby unitsis little different from that of the example shown in FIG. 1 or 9.

For example, in a case that the re-measurement by the same analysis unitis needed relating to the sample rack in the standby unit 20B attachedto the analysis unit 100B, the sample rack is moved from the standbyunit 20B to the returning line 65, and is moved to the racktransportation line 60 near the entrance of the standby unit 20A, andagain stops at the sample sampling position of the analysis unit 100B(upper the transportation line 60) so as to be sampled.

If the sample on the sample rack in the standby unit 20B does not needto be re-measured, the sample rack is moved from the standby unit 20B tothe rack transportation line 60, and is transferred to the samplesampling position of the biochemical analysis unit 200A, for example. Inthis case, the sample rack does not passes by the returning line 65.

1. An analysis apparatus for a body liquid sample comprising a rackintroducing unit for introducing a sample rack having a sample; aplurality of analysis units for analysis-processing the sample; and arack transporting apparatus for transporting the sample rack coming outfrom said rack introducing unit to at least one of said plurality ofanalysis units, which further comprises: a first analysis unit a firstpipetting device using a disposable nozzle tip and a second analysisunit having a second pipetting device using a repetitively used pipettenozzle, said first analysis unit and said second analysis unit beingincluded in said plurality of analysis units; and a memory unit forstoring a specified analysis item necessary for sample sampling by saidnozzle tip, said sample rack having a sample to be analyzed on saidspecified analysis item being transported to said first analysis unitbefore being transported to the other analysis units to be executedsample sampling for said specified analysis item using said nozzle tip.2. An analysis apparatus for a body liquid sample according to claim 1,which further comprises: a display unit for displaying a screen forspecifying said specified analysis item; and a control unit forrecognizing a sample including said specified analysis item among aplurality of analysis items instructed to be analyzed and controllingsaid rack transporting apparatus so that a sample rack having saidrecognized sample is transported to said first analysis unit in firstplace of sample sampling processing.
 3. An analysis apparatus for a bodyliquid sample according to claim 2, wherein said screen displayed bysaid display unit comprises an analysis item selecting section capableof selecting one or more analysis items out of a plurality of analysisitems; and a level selecting section capable of instructing an avoidinglevel of carry-over corresponding to the selected analysis item.
 4. Ananalysis apparatus for a body liquid sample according to claim 1,wherein said plurality of analysis units are arranged along atransporting path of said rack transporting apparatus, and a sample rackhaving samples not requiring analysis of said specified analysis item istransported so as to be let drop in at said plurality of analysis unitsin arranging order depending on necessity.